The present invention relates to the vaccination of cats, dogs, livestock and fur-bearing animals against contagious infections caused by dermatophytes. A novel, broad spectrum vaccine has been prepared comprising a suspension of mycelial elements and spores of four "killed" dermatophytes (Trichophyton equinum, Trichophyton mentagrophytes (var. granulare), Microsporum canis and Microsporum gypseum) along with an adjuvant (i.e., immunologic stimulator) that enhances the vaccine's effectiveness. The vaccine is effective in the prophylaxis of infections resulting from the animal's contact with T. equinum, T. mentagophytes, M. canis, and M. gypseum, major dermatophytic pathogens of animals. Cross immunity against T. verrucosum and M. equinum is also stimulated by this vaccine.
A. Field of the Invention
Dermatophytoses are contagious, infectious diseases of man and other mammals caused by a group of keratinophilic, parasitic fungi known as "dermatophytes." Although they are not debilitating or fatal, dermatophytoses are among the most prevalent of human and animal infectious diseases. Millions of adults and children in the United States suffer from one or more types of dermatophyte infection. The dermatophytes that characteristically infect animals (i.e., zoophilic dermatophytes) are highly contagious; they persist in the environment as infectious spores for years, and they often transfer from infected animals to their human attendants as zoonotic infections. As a result, they constitute a substantial public health hazard.
Dermatophyte infections can affect various keratinized tissues, such as the hair and stratum corneum of the skin causing areas of hair loss, scaliness and cutaneous inflammation. The most frequent dermatophyte infection in animals is called "ringworm" (i.e., infections of the skin or hair); the most frequent dermatophyte infection in man is "athlete's foot" (i.e., infections of that appendage). These diseases are a consequence of the host animal's reaction to the dermatophyte as well as the invasion of the animal's tissues by the fungus. Although the disease can generally be treated, treatment may take weeks or months to completely resolve the condition. Ringworm is unsightly, at best, and in severe cases can result in the generation of disfiguring scar tissue. It has been estimated in recent years that approximately $150,000,000 is spent annually in the United States on the treatment of ringworm.
Ringworm infections in humans and animals can be caused by a number of dermatophytes that reside on various animals, including pets such as dogs and cats, fur-bearing animals (e.g., rabbits and mink) and livestock, such as horses, cattle and pigs. Hair and other skin fragments or debris infected with dermatophytes are lost by infected animals and contaminate the premises where these animals are maintained. Contamination may last for as much as four years. People, such as handlers, who come in contact with the animals or the premises can become carriers for the fungus to other animals or humans. Because ringworm is a world-wide problem and is transmitted between animals and man, the World Health Organization has attempted to diminish the contacting of viable dermatophytes by persons handling animals through reduction of the incidence of infection in animal populations.
In addition to the health consequences to man, the incidence of dermatophyte infections in animals can cause serious consequences for animal owners. Animals infected with dermatophytes are excluded from the sale or show ring and from competitive events, such as horse races. Because dermatophyte infections spread rapidly among animals, entire herds, kennels or stables full of animals may be involved when infection in one or more animals is observed. In animals bred for their meat, infection with dermatophytes may result in a diminished rate of weight gain. Although griseofulvin administered orally or as a feed additive may be used to treat certain types of infected animals, it can be prohibitively expensive where an entire herd is involved, and it may also raise concerns if the animals are used to supply meat or dairy products for human consumption.
In particular, ringworm on cats and dogs caused by M. canis and other dermatophytes is a highly contagious infection among those animals and is readily transmissible to humans. Dermatophytoses is easily transmitted by the movement of infectious hair or scales directly from one animal to another or through intermediate contact with physical items, such as wooden fixtures, grooming brushes, carpets, bedding and any other physical items of common contact. Transmission is especially accelerated by wild or stray cats, dogs and rodents that come into contact with household pets. Pedigreed cats and dogs and livestock infected by dermatophytoses are banned from show arenas and may be barred from crossing state or international boundaries. It is important both to the owners of those animals and to the public at large to control dermatophytoses in these animals.
B. Description of the Prior Art
Because dermatophytes are wide spread parasitic agents and because infection eventually engenders acquired immunity in affected individuals, prophylactic use of immunizing agents is indicated to reduce the susceptibility of animals and humans to infection. It is recognized, however, that:
[n]o subject in the field of medical mycology has evoked more controversy than "immunity and resistance" in dermatophyte infections. The voluminous literature begins in the early nineteen hundreds and continues to accumulate unabated to the present day . . . . There is no single, clear-cut mechanism that will explain all aspects of susceptibility and immunity to dermatophyte infection. (Rippon, "Medical Mycology: the Pathogenic Fungi and the Pathogenic Actinomycetes," W. B. Saunders Company (3rd Ed. 1988), p. 231.)
As reported in Rippon, immunization by injection of live or killed fungi, their extracts, or their metabolic products has been attempted many times in animals. However, the author notes that the challenge with a homologous organism results only in attenuation of the disease. Resistance is transitory only, and complete susceptibility returns after a few months. Rippon's conclusions appear to be based in whole or in part on A. W. Lepper, "Immunological Aspects of Dermatomycoses in Animals and Man," Rev. Med. Vet Mycol., 6:432-42 (1969), which itself is a review of the literature on dermatophyte immunity. See also, S. F. Grappel, "Immunology of Dermatophytes and Dermatophytosis," Bacteriological Reviews, 38:222-50 (1974).
Prior to the present invention, there has been no commercially practicable vaccine for the prevention of ringworm in dogs, cats, livestock and fur-bearing animals. Prophylaxis of T. equinum infection in horses using a viable vaccine comprising a suspension of T. equinum material is disclosed in U.S. Pat. No. 4,229,434 to Sarkisov et al. However, there are several defects with that vaccine. First, because it is viable, the vaccine of Sarkisov et al. may cause localized infection at the injection site. Second, because the vaccine is live, it cannot be incorporated with other adjuvant materials frequently utilized in vaccines to enhance immunologic response. Finally and of most significance, there are serious concerns about the infection of handlers and other animals contacted externally with the vaccine, since the vaccine contains "live," i.e., active T. equinum. For that reason, the vaccine has not been approved for use in certain European countries and the United States.
In addition, U.S. Pat. No. 4,368,191 to Sarkisov et al. discloses a vaccine for the prophylaxis and treatment of trichophytosis caused by T. mentagrophytes. The patent mentions the risks to humans associated with the study and use of a vaccine comprising live, virulent T. gypseum (i.e., a variety of T. mentagrophytes). It attempts to overcome these health risks by using a vaccine of live T. gypseum of a specific strain with "weak virulence."
The live vaccine disclosed in this Sarkisov et al. patent is limited to the prophylaxis from infection by the homologous dermatophyte on which the vaccine is based. No cross-immunity or resistance to infection from other dermatophytes is disclosed.
At the present time, there is no known broad spectrum vaccine for prophylaxis of a variety of dermatophyte infections in dogs, cats, livestock and fur-bearing animals which is effective and does not pose a risk of infection to handlers and animals contacted externally with the vaccine.